Arylaminopropanone derivatives as potential cholinesterase inhibitors: Synthesis, docking study and biological evaluation

KUBÍNOVÁ, RENATA; ENRIZ, DANIEL; KROUTIL, ALE?; GUTIERREZ, LUCAS J.; CSÖLLEI, JOZEF; HUDCOVÁ, ANNA; GARRO, ADRIANA D.; ORAVEC, MICHAL

MOLECULES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2020 vol. 25

1420-3049

Neurodegenerative diseases in which the decrease of the acetylcholine is observed are growing worldwide. In the present study, a series of new arylaminopropanone derivatives with N-phenylcarbamate moiety (1-16) were prepared as potential acetylcholinesterase and butyrylcholinesterase inhibitors. In vitro enzyme assays were performed; the results are expressed as a percentage of inhibition and the IC50 values. The inhibitory activities were compared with reference drugs galantamine and rivastigmine showing piperidine derivatives (1-3) as the most potent. A possible mechanism of action for these compounds was determined from a molecular modelling study by using combined techniques of docking, molecular dynamics simulations and quantum mechanics calculations.